title: Effects of mitiglinide, a short-acting insulin secretagogue, on daily glycemic variability and oxidative stress markers in Japanese patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  The objective of this study was to clarify the effects of mitiglinide on daily glycemic variability and oxidative stress markers in outpatients with type 2 diabetes mellitus that is insufficiently controlled by diet and/or non-insulin secretagogues.
  
  
  METHODS
  We enrolled 24 patients with type 2 diabetes whose glycemic control had been suboptimal [i.e. glycosylated hemoglobin (HbA(1c)) ≥ 6.9 %]. The patients were treated with mitiglinide 10 mg three times daily for 16 weeks. If their glycemic control was not improved at week 8, the dose of mitiglinide was increased to 20 mg three times daily. Daily glycemic variability was assessed by 7-point self-monitoring of blood glucose for 2 days, and standard deviation (SD), M value, and mean of daily differences(MODD) were calculated. Oxidative stress was assessed by oxidized low-density lipoprotein, pentosidine,urinary 8-iso-prostaglandin F2 alpha, and urinary 8-hydroxydeoxy guanosine.
  
  
  RESULTS
  After 16 weeks of mitiglinide treatment, the HbA(1c) level was significantly decreased (mean ± SD,7.4 ± 0.7 to 6.8 ± 0.5 %, P < 0.0001). Postprandial glucose excursion and glycemic variability were also significantly improved after mitiglinide treatment (all P < 0.05). The reductions in SD, M value, and MODD were 17, 50,and 48 %, respectively. There was a significant positive correlation between the change in HbA(1c) and change in SD during the study (r = 0.454, P = 0.03). There were no significant changes in oxidative stress markers.
  
  
  CONCLUSIONS
  The present study supports the notion that mitiglinide improves postprandial glucose excursion and HbA(1c) level in patients with type 2 diabetes. In addition,we demonstrated that mitiglinide also effectively improves daily glycemic variability. The effect of mitiglinide on oxidative stress needs further investigation.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kodani
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saisho
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D054833:Isoindoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007564:Japan; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054833:Isoindoles; C517652:hemoglobin A1c protein, human; C087255:mitiglinide